JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-15
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IF 9.429
Xu Li,Sun Zichen,Xing Zhiyao,Liu Yutong,Zhao Hongting,Tang Zhongmin,Luo Yu,Hao Shuangying,Li Kuanyu
Abnormal iron metabolism, mitochondrial dysfunction and the derived oxidative damage are the main pathogeneses of Friedrich's ataxia (FRDA), a single-gene inherited recessive neurodegenerative disease characterized by progressive cerebellar and sensory ataxia. This disease is caused by frataxin (FXN) mutation, which reduces FXN expression and impairs iron sulfur cluster biogenesis. To date, there is no effective therapy to treat this condition. Curcumin is proposed harboring excellent ability to resist oxidative stress through Nrf2 activation and its newly found ability to chelate iron. However, its limitation is its poor water solubility and permeability. Here, we synthesized slow-release nanoparticles (NPs) by loading curcumin (Cur) into silk fibroin (SF) to form NPs with an average size of 150 nm (Cur@SF NPs), which exhibited satisfactory therapeutic effects on the improvement of FRDA manifestation in lymphoblasts (1 μM) derived from FRDA patients and in YG8R mice (150 mg/kg/5 days). Cur@SF NPs not only removed iron from the heart and diminished oxidative stress in general but also potentiate iron-sulfur cluster biogenesis, which compensates FXN deficiency to improve the morphology and function of mitochondria. Cur@SF NPs showed a significant advantage in neuron and myocardial function, thereby improving FRDA mouse behavior scores. These data encourage us to propose that Cur@SF NPs are a promising therapeutic compound in the application of FRDA disease.Graphical Abstract
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CELLULAR AND MOLECULAR LIFE SCIENCES
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2023
·Vol. 80
·期 3
·1-16
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IF 8
Li Xiaoxue,Zhang Yumeng,Chang Jianghao,Zhang Chenglin,Li Lin,Dai Yifan,Yang Haiyuan,Wang Ying
Previous studies have shown that mfat-1 transgenic mice have protective effects against some central nervous system (CNS) disorders, owing to the high docosahexaenoic acid (DHA) content enriched in their brains. However, whether this protective effect is connected to the blood – brain barrier (BBB) remains unclear. This study aims to investigate the mechanisms of the protective effect against hypoxic-ischemic brain damage (HIBD) of mfat-1 transgenic mice. mfat-1 mice not only demonstrated a significant amelioration of neurological dysfunction and neuronal damage but also partly maintained the physiological permeability of the BBB after HIBD. We initially showed this was associated with elevated major facilitator superfamily domain-containing 2a (Mfsd2a) expression on the BBB, resulting from more lysophosphatidylcholine (LPC)-DHA entering the brain. Wild-type (WT) mice showed a similar Mfsd2a expression trend after long-term feeding with an LPC-DHA-rich diet. Knockdown of Mfsd2a by siRNA intra-cerebroventricular (ICV) injection neutralized the protective effect against HIBD-induced BBB disruption in mfat-1 mice, further validating the protective function of Mfsd2a on BBB. HIBD-induced BBB high permeability was attenuated by Mfsd2a, primarily through a transcellular pathway to decrease caveolae-like vesicle-mediated transcytosis. Taken together, these findings not only reveal that mfat-1 transgenic mice have higher expression of Mfsd2a on the BBB, which partly sustains BBB permeability via vesicular transcytosis to alleviate the severity of HIBD, but also suggest that dietary intake of LPC-DHA may upregulate Mfsd2a expression as a novel therapeutic strategy for BBB dysfunction and survival in HIBD patients.
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APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2021
·Vol. 195
·期 4
·2432-2450
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IF 2.926
Zhang Yueqi,Ding Liping,Yan Zhenzhen,Zhou Dandan,Jiang Junwei,Qiu Jiarong,Xin Zhihong
An alkaline esterase, designated as EstXT1, was identified through functional screening from a metagenomic library. Sequence analysis revealed that EstXT1 belonged to the family VIII carboxylesterases and contained a characteristic conserved S-x-x-K motif and a deduced catalytic triad Ser56-Lys59-Tyr165. EstXT1 exhibited the strongest activity toward methyl ferulate at pH 8.0 and temperature 55°C and retained over 80% of its original activity after incubation in the pH range of 7.0–10.6 buffers. Biochemical characterization of the recombinant enzyme showed that it was activated by Zn 2+ and Co 2+ metal ion, while inhibited by Cu 2+ and CTAB. EstXT1 exhibited significant promiscuous acyltransferase activity preferred to the acylation of benzyl alcohol acceptor using short-chain p NP-esters (C2-C8) as acyl-donors. A structure–function analysis indicated that a WAG motif is essential to acyltransferase activity. This is the first report example that WAG motif plays a pivotal role in acyltransferase activity in family VIII carboxylesterases beside WGG motif. Further experiment indicated that EstXT1 successfully acylated cyanidin-3-O-glucoside in aqueous solution. The results from the current investigation provided new insights for the family VIII carboxylesterase and lay a foundation for the potential applications of EstXT1 in food and biotechnology fields.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2018
·Vol. 410
·期 23
·5871-5878
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IF 3.307
Wang Yu,Cui Min,Jiao Mingxia,Luo Xiliang
Accurate detection of protein biomarkers in complex media remains a challenge due to severe nonspecific adsorption and biofouling, and sensing interfaces that combine the high sensitivity and antifouling ability are highly desirable. Herein, an antifouling sensing interface capable of sensitively assaying immunoglobulin E (IgE) in biological samples was constructed. The sensing interface was fabricated through the self-assembly of a zwitterionic peptide and the IgE aptamer onto a macroporous Au substrate, which was electrochemically fabricated with the aid of multilayer polystyrene nanospheres self-assembled on glassy carbon electrode. Due to the huge surface area arising from porous morphology and high specificity of aptamer, the developed electrochemical biosensor exhibits ultrahigh sensitivity and selectivity towards IgE, with the linear range of 0.1–10 pg mL −1 , and a very low limit of detection down to 42 fg mL −1 . Interestingly, owing to the presence of the zwitterionic peptide, the biosensing interface can satisfyingly reduce the nonspecific adsorption and fouling effect. Consequently, the biosensor was successfully applied to detect IgE in complex biological samples, indicating great promise of this peptide-based sensing interface for antifouling assays.
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MICROCHIMICA ACTA
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2018
·Vol. 185
·期 3
·1-9
·
IF 5.705
Wang Wei,Jayachandran Silambarasan,Li Mengru,Xu Shenghao,Luo Xiliang
An electrochemical biosensor for the detection of microRNA was prepared via chemical grafting of a Methylene Blue labeled reporter (MB-Rep) duplex onto a nanostructured surface that was obtained by electrodeposition of cobalt oxide and poly(o-phenylenediamine). This is followed by the attachment of hyaluronic acid and gold nanoclusters. In the presence of the target (microRNA), the probe-target duplex and the MB-Rep hairpin are formed. These will displace the labeled reporter from the sensor surface, and this results in a decrease of the amperometric signal for MB at a typical working voltage of −0.28 V (vs. Ag/AgCl). The electrode modified with hyaluronic acid possesses a large electroactive surface area and an excellent antifouling property. This makes it useful for ultrasensitive quantitation of microRNA even in complex biological media. The sensor has a linear response in the 100 f. to 0.1 μM microRNA concentration range, and a 33.3 f. detection limit. It was successfully applied to the determination of microRNA in cancer cells.
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Nature Communications
·
2025
·Vol. 17
·期 1
·88
·
IF 15.7
Zhang Peng,Chen Dinghao,Fang Yu,Li Sangshuang,Zhou Ziao,Lu Huanfen,Cheng Jianjun,Wang Huaimin
Osteoporosis therapies remain limited by non-specific osteoclast inhibition, which disrupts physiological bone remodeling and increases fracture risk. Here we show that selectively targeting mature osteoclasts via enzyme-responsive nanoparticles could eliminate pathological bone resorption while generating apoptotic bodies (ABs) to promote regeneration. We design OsteoSAVE, a peptide-based nanoparticle integrating a cathepsin K (CTSK)-cleavable linker, a bone-targeting motif, and a self-assembling biphenyl core. Upon CTSK-mediated hydrolysis, OsteoSAVE transforms into nanofibers within osteoclast lysosomes, inducing apoptosis and releasing ABs enriched with PDGF-BB. Mechanistic studies confirm CTSK-selective cleavage and charge-driven cellular specificity. In ovariectomized mice, OsteoSAVE restores bone density by coupling osteoclast elimination with ABs-mediated osteogenesis via PI3K/AKT activation in mesenchymal stem cells. This work establishes enzyme-triggered supramolecular self-assembly as a paradigm for dual-action therapies that recalibrate bone homeostasis without disrupting physiological processes.
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FOOD SCIENCE AND BIOTECHNOLOGY
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2025
·
IF 3.1
Park Chan-Hyeok,Ganbat Chinbat,Han Jung-Ah
Orally disintegrating films (ODFs) were prepared from five natural polymers—starch (STA), hyaluronic acid (HA), pectin (PEC), chitosan (CHI), and gelatin (GEL)—using literature‑based, polymer‑specific protocols. All films were cast to a uniform thickness of 1.00 ± 0.01 mm and then evaluated for physicochemical, mechanical, and dissolution properties, alongside a sensory assessment. STA, PEC, and CHI required glycerol as a plasticizer and consequently showed higher moisture contents, whereas GEL and HA formed stable films without plasticizers and exhibited higher tensile strength (51.70 and 76.77 MPa). STA displayed the highest opacity, moisture content (25.44%), and water‑vapor permeability (6.63 g·mm·m -2 ·h -1 ·kPa -1 ), indicating lower storage stability. Vitamin C release was fastest from PEC and GEL and slowest from HA; STA and CHI showed marked pH‑dependent dissolution. Sensory results mirrored instrumental trends: PEC was most preferred for rapid intraoral disintegration, whereas CHI was least favored. Overall, hydrocolloid selection governed water management, disintegration, and release profiles, directly linking material design with consumer‑relevant performance and offering guidance for polymer choice in functional‑food ODFs.
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JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 24
·期 1
·113
·
IF 12.6
Guan Shujuan,Yang Ruyue,Deng Danning,Long Huilin,Ou Zihao,Ge Xiaoxue,Jiang Xiujuan,Hu Xiumei,Chen Dingqiang
Bloodstream infections (BSIs) are life-threatening conditions with rising mortality, urgently requiring rapid pathogen identification to guide timely antibiotic therapy. Current methods (phenotypic identification, MALDI-TOF MS, molecular techniques) are faced with limitations in cost, turnaround time and accessibility. In this study, it was discovered that the drying of microbial suspensions on slides could lead to species-specific desiccation patterns, which reflects the physicochemical properties and complex interactions of microorganisms during evaporation. Inspired by this interesting phenomenon, an AI-powered platform is proposed for rapid pathogen identification through automated analysis of these patterns. By establishing an image dataset comprising 10,055 desiccation patterns of common BSIs pathogens ( Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecium and Candida albicans ), a ResNet-34 deep learning model is trained, achieving a classification accuracy of 91.8% and an area under the receiver operating characteristic curve (AUC-ROC) of 0.99. Following pure culture, identification is completed within 5 min after a simple drying step at 40 °C. With its minimal sample requirement, low cost, and operational simplicity, this platform demonstrates significant potential as a point-of-care diagnostic tool, particularly in resource-constrained regions. This technology offers a promising strategy to combat BSIs and improve patient outcomes. Graphical
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Nature Communications
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2025
·
IF 15.7
Yinglan Yu,Yongfeng Xu,Zehui Yu,Xinrui Liu,Jiayue Guo,Min Xiang,Junmeng Chen,Riyanto Teguh Widodo,Lei Luo
Oral antibiotics are a mainstay for treating bacterial infections, but unabsorbed portions can reach the caecum and colon, leading to gut dysbiosis. Herein, we engineer a biohybrid delivery system through the integration of milk extracellular vesicles with liposomes. The hybrid vesicles employ targeting mechanisms via neonatal Fc receptor and peptide transporter 1, facilitating antibiotic transport across the proximal small intestine. These vesicles exhibit superior drug encapsulation efficiency, stable release behavior, efficient mucus traversal, higher endocytosis, increased basolateral exocytosis, and improved oral absorption, achieving a 3.24-fold increase in oral bioavailability compared to free antibiotics. In lung bacterial infections and bacteremia models, hybrid vesicle-encapsulated cefdinir outperforms free antibiotics in eliminating infections. Notably, this approach also mitigates adverse effects on the intestinal microbiota, safeguarding the animals from dysbiosis-associated metabolic syndromes and opportunistic pathogen infections. This innovative hybrid vesicle system holds promise for the oral delivery of other drugs that suffer from limited absorption or cause gut dysbiosis. In this work, authors present a biohybrid delivery system aimed at overcoming low oral bioavailability and antibiotic-induced dysbiosis by enabling efficient antibiotic transport in the proximal small intestine.
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Clinical Epigenetics
·
2025
·Vol. 18
·期 1
·12
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IF 4.4
Yu Chao,Yao Liyuan,Du Xinyu,Yu Jianjun,Wang Yanjin,Hou Xiying,Shen Fengchen,Liu Na,Zhuang Shougang
Background Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase that catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3), has been implicated in promoting renal fibrogenesis. Nevertheless, its precise role and underlying mechanisms remain incompletely defined. Methods To investigate the role of EZH2 in partial epithelial-mesenchymal transition (pEMT) and renal fibrosis, we utilized a mouse model with renal tubular cell-specific EZH2 deletion and administered gambogic acid (GA), a selective EZH2 degrader, following unilateral ureteral obstruction (UUO). In vitro, mouse renal epithelial cells were stimulated with TGF-β1 and treated with either EZH2-specific siRNA or GA to assess the effects on EMT and Notch1/3 signaling. In addition, chromatin immunoprecipitation (ChIP) assays were conducted to evaluate the binding of EZH2 and H3K27me3 to the promoters of Notch1 and Notch3. Results Compared with wild-type controls, mice with tubular cell-specific EZH2 deletion exhibited significantly reduced renal fibrosis, characterized by decreased expression of fibronectin, collagen III, vimentin, and Snail, while preserving E-cadherin levels in injured kidneys. Pharmacological degradation of EZH2 with GA produced comparable antifibrotic effects. UUO injury markedly upregulated Notch1, Notch3, the Notch intracellular domain, Hes1, Hey2, and Jagged-1; these increases were significantly suppressed by either EZH2 deletion or GA treatment. Similarly, in vitro, GA or EZH2-specific siRNA inhibited the expression of Notch signaling molecules in TGF-β1–treated renal epithelial cells. Chromatin immunoprecipitation analyses revealed direct binding of EZH2 and H3K27me3 to the Notch1 and Notch3 promoters. UUO injury enhanced EZH2 binding while reducing H3K27me3 enrichment at these sites, effects reversed by GA treatment. Conclusions These findings demonstrate that epithelial EZH2 contributes to pEMT in renal tubular cells and promotes renal fibrosis, at least in part through activation of Notch signaling. Targeting EZH2 may hold potential as a therapeutic approach for chronic kidney disease.
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EMBO Molecular Medicine
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2025
·Vol. 18
·期 1
·275
·
IF 8.3
Huanhuan Gao,Yuecheng Zhan,Yuanqi Liu,Zhiyi Zhu,Yuxiu Zheng,Liqin Qian,Zhangzhi Xue,Honghan Cheng,Zongxiang Nie,Weigang Ge,Senlin Ruan,Jiaxu Liu,Jikai Zhang,Yingying Sun,Lei Zhou,Dongyue Xun,Yingrui Wang,Heyun Xu,Huiwen Miao,Yi Zhu,Tiannan Guo
Circulating blood proteomics enables minimally invasive biomarker discovery. Nanoparticle-based circulating plasma proteomics studies have reported varying number of proteins (ca 2000–7000), but it remains unclear whether a higher protein number is more informative. Here, we first develop OmniProt—a silica-nanoparticle workflow optimized through a systematic evaluation of nanoparticle types and protein corona formation parameters. Next, we present an Astral spectral library for 10,109 protein groups. Using the Astral with 60 sample-per-day throughput, OmniProt identifies ca 3000 to 6000 protein groups from human plasma. Platelet/erythrocyte/coagulation-related contamination artificially inflates protein identifications and compromises quantification accuracy in nanoparticle-enriched samples. Through controlled contamination experiments, we identified biomarkers for platelet/erythrocyte/coagulation-related contamination in nanoparticle-based plasma proteomics. We developed open-access software Baize for contamination assessment. We validated the pipeline in 193 patients with CT-indistinct benign nodules or early-stage lung cancers, flagging five contaminated samples. This study reveals that contamination alters protein identification/quantification in nanoparticle-based plasma proteomics and presents Baize software to evaluate it. In mass spectrometry-based plasma proteomics, blood platelet and erythrocyte contamination artificially inflates protein identification and compromises quantification. An open-source software, Baize, is developed to systematically evaluate this critical issue. In mass spectrometry-based plasma proteomics with nanoparticle enrichment, blood platelet and erythrocyte contamination artificially inflates protein identification and compromises quantification. The open-source software Baize is developed to systematically evaluate this critical issue.
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Journal of Neuroinflammation
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2022
·Vol. 19
·期 1
·1-15
·
IF 9.587
Wang Huidi,Zhang Mingsi,Li Jie,Liang Jianhai,Yang Mengjia,Xia Genghong,Ren Yueran,Zhou Hongwei,Wu Qiheng,He Yan,Yin Jia
Background Poststroke cognitive impairment (PSCI) is prevalent in stroke patients. The etiology of PSCI remains largely unknown. We previously found that stroke induces gut microbiota dysbiosis which affects brain injury. Hereby, we aimed to investigate whether the gut microbiota contributes to the pathogenesis of PSCI.Methods 83 stroke patients were recruited and their cognitive function were measured by Montreal Cognitive Assessment (MoCA) scores 3 months after stroke onset. The peripheral inflammatory factor levels and gut microbiota compositions of the patients were analyzed. Fecal microbiota transplantation from patients to stroke mice was performed to examine the causal relationship between the gut microbiota and PSCI. The cognitive function of mice was evaluated by Morris water maze test.Results 34 and 49 stroke patients were classified as PSCI and non-PSCI, respectively. Compared with non-PSCI patients, PSCI patients showed significantly higher levels of gut Enterobacteriaceae, lipopolysaccharide (LPS) and peripheral inflammation markers. Consistently, stroke mice that received microbiota from PSCI patients (PSCI mice) presented a higher level of Enterobacteriaceae, intestinal Toll-like receptor-4 (TLR4) expression, circulating LPS, LPS-binding protein (LBP) and inflammatory cytokines, and a lower level of fecal butyrate, severer intestine destruction and cognitive impairment than mice that received microbiota from nPSCI patients (nPSCI mice). In addition, we observed exacerbations in blood–brain barrier (BBB) integrity, microglial activation, neuronal apoptosis in the CA1 region of the hippocampus, and Aβ deposition in the thalamus of PSCI mice in comparison with nPSCI mice. Intraperitoneal injection of LPS after stroke caused similar pathology to those seen in PSCI mice. Supplementation with sodium butyrate (NaB) via drinking water rescued these detrimental changes in PSCI mice.Conclusion sOur data indicate a cause–effect relationship between gut microbiota and PSCI for the first time, which is likely mediated by inflammation-regulating metabolites including LPS and butyrate.
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